Structural genomic variation in ischemic stroke

Mar Matarin, Javier Simon-Sanchez, Hon Chung Fung, Sonja Scholz, J. Raphael Gibbs, Dena G. Hernandez, Cynthia Crews, Angela Britton, Fabienne Wavrant De Vrieze, Thomas G Brott, Robert D Jr. Brown, Bradford B. Worrall, Scott Silliman, L. Douglas Case, John A. Hardy, Stephen S. Rich, James F Meschia, Andrew B. Singleton

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions; 3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalNeurogenetics
Volume9
Issue number2
DOIs
StatePublished - May 2008

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Genomic Structural Variation
Stroke
Genome
Single Nucleotide Polymorphism
Genome-Wide Association Study
Genetic Association Studies
Molecular Biology
Mutation

Keywords

  • Cerebral ischemia
  • Copy number variants
  • Genetics
  • Stroke

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

Matarin, M., Simon-Sanchez, J., Fung, H. C., Scholz, S., Gibbs, J. R., Hernandez, D. G., ... Singleton, A. B. (2008). Structural genomic variation in ischemic stroke. Neurogenetics, 9(2), 101-108. https://doi.org/10.1007/s10048-008-0119-3

Structural genomic variation in ischemic stroke. / Matarin, Mar; Simon-Sanchez, Javier; Fung, Hon Chung; Scholz, Sonja; Gibbs, J. Raphael; Hernandez, Dena G.; Crews, Cynthia; Britton, Angela; Wavrant De Vrieze, Fabienne; Brott, Thomas G; Brown, Robert D Jr.; Worrall, Bradford B.; Silliman, Scott; Case, L. Douglas; Hardy, John A.; Rich, Stephen S.; Meschia, James F; Singleton, Andrew B.

In: Neurogenetics, Vol. 9, No. 2, 05.2008, p. 101-108.

Research output: Contribution to journalArticle

Matarin, M, Simon-Sanchez, J, Fung, HC, Scholz, S, Gibbs, JR, Hernandez, DG, Crews, C, Britton, A, Wavrant De Vrieze, F, Brott, TG, Brown, RDJ, Worrall, BB, Silliman, S, Case, LD, Hardy, JA, Rich, SS, Meschia, JF & Singleton, AB 2008, 'Structural genomic variation in ischemic stroke', Neurogenetics, vol. 9, no. 2, pp. 101-108. https://doi.org/10.1007/s10048-008-0119-3
Matarin M, Simon-Sanchez J, Fung HC, Scholz S, Gibbs JR, Hernandez DG et al. Structural genomic variation in ischemic stroke. Neurogenetics. 2008 May;9(2):101-108. https://doi.org/10.1007/s10048-008-0119-3
Matarin, Mar ; Simon-Sanchez, Javier ; Fung, Hon Chung ; Scholz, Sonja ; Gibbs, J. Raphael ; Hernandez, Dena G. ; Crews, Cynthia ; Britton, Angela ; Wavrant De Vrieze, Fabienne ; Brott, Thomas G ; Brown, Robert D Jr. ; Worrall, Bradford B. ; Silliman, Scott ; Case, L. Douglas ; Hardy, John A. ; Rich, Stephen S. ; Meschia, James F ; Singleton, Andrew B. / Structural genomic variation in ischemic stroke. In: Neurogenetics. 2008 ; Vol. 9, No. 2. pp. 101-108.
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AU - Hernandez, Dena G.

AU - Crews, Cynthia

AU - Britton, Angela

AU - Wavrant De Vrieze, Fabienne

AU - Brott, Thomas G

AU - Brown, Robert D Jr.

AU - Worrall, Bradford B.

AU - Silliman, Scott

AU - Case, L. Douglas

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AU - Rich, Stephen S.

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